Abstract

The electrophysiological actions of several agonists which may differentiate between P2X1- and P2X3-receptors were studied under concentration and voltage-clamp conditions in dissociated neurones of 1-4 day old rat dorsal root ganglia. β,γ-Methylene-D-ATP (β,γ-me-D-ATP) (1-300 μM), diadenosine 5',5'''-P1,P5-pentaphosphate (AP5A) (100 nM-300 μM), diadenosine 5',5'''-P1,P4-tetraphosphate (AP4A) (300 nM-300 μM) and uridine 5'-triphosphate (UTP) (1 μM-1 mM) all activated concentration-dependent inward currents with a latency to onset of a few ms. The concentration-response curves for β,γ-me-D-ATP and AP5A and ATP had similar maximum values, while that for AP4A had a lower maximum. The concentration-response curve to UTP was shallow and did not reach a maximum. β,γ-Methylene-L-ATP was virtually inactive. The rank order of agonist potency was ATP>AP5A∼amp;AP4A>β,γ-me-D-ATP>UTP>>β,γ-methylene-L-ATP. The inward currents were inhibited by the P2-receptor antagonists suramin (100 μM) and pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) (10 μM). PPADS also inhibited responses to ATP (800 nM) and α,β-methylene ATP (2 μM) in a concentration-dependent manner. This study shows that β,γ-me-D-ATP, AP5A, AP4A and UTP all act via a suramin- and PPADS-sensitive P2X-receptor to evoke rapid, transient inward currents in dissociated neurones of rat dorsal root ganglia. The very low activity of β,γ-methylene-L-ATP suggests that the agonists were acting at the P2X3-subtype to produce these effects.